Red Lesions on Forearm

Cutaneous sarcoidosis refers to the skin manifestations of sarcoidosis, a chronic granulomatous disorder known to affect the lungs, lymph nodes, and other organs.1 Cutaneous involvement occurs in about one-quarter of patients with sarcoidosis, often as the initial presentation of systemic...

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Cutaneous sarcoidosis refers to the skin manifestations of sarcoidosis, a chronic granulomatous disorder known to affect the lungs, lymph nodes, and other organs.¹ Cutaneous involvement occurs in about one-quarter of patients with sarcoidosis, often as the initial presentation of systemic disease.¹

The earliest observation of sarcoidosis is credited to British dermatologist Jonathan Hutchinson, who described painless purple lesions on the skin of a coal wharf worker in 1869.² A quarter of a century later, Hutchison reported erythematous skin lesions on the face and forearms of a woman with the surname Mortimer and dubbed the skin findings Mortimer’s malady. He noted the absence of ulcerating or crusting in these lesions, which differentiated them from those of tuberculosis or lupus.² Shortly afterward, in 1897, Norwegian dermatologist Caesar Boeck presented the pathology of nodular lesions resembling Mortimer’s skin findings. Referencing the condition’s sarcoma-like presentation, Boeck referred to the disease as multiple benign sarkoid of the skin and, therefore, the term sarcoidosis was born.²

The epidemiology of sarcoidosis varies by race, gender, and geographic location with the incidence ranging from 1.4 per 100,000 people in Spain and Japan to 64 per 100,000 in Scandinavia.^3,4 In the US, Black individuals are at greater risk for sarcoidosis than White individuals; reported incidences are 35.5 per 100,000 and 10.9 per 100,000 in Black and White individuals, respectively.⁴ Black patients are also prone to have a more severe disease course marked by rapid progression and higher frequency of relapse.⁴ Compared with men, women tend to have a slightly greater risk for sarcoidosis across different races and age groups.^3,4 The disorder also exhibits a bimodal age distribution, with separate peaks among patients in their 30s and 60s.⁴

Although extensive research has been conducted on sarcoidosis, its etiology remains elusive. A broad characterization of the disease process is that host factors and infectious and noninfectious environmental factors trigger systemic granulomatous inflammation in genetically susceptible individuals that presents as a heterogeneous group of disorders.⁵ Potential triggers include infectious agents, such as mycobacteria and Propionibacterium acnes. The role of exposure to various chemicals and metals in the etiology of sarcoidosis also has been debated.⁵ Sarcoid antigens are presented to CD4+ T cells via major histocompatibility complex class II molecules, leading to a type 1 helper (TH1) cell–predominant immune cascade and granulomatous inflammation in target organs.⁵

The exact cause of sarcoidosis has yet to be determined, but given the racial predilection and familial clustering of disease, risk factors for sarcoidosis include race, family history, and genetics.^5.6 Genome-wide association studies have identified human leukocyte antigen (HLA) alleles associated with higher risk of developing sarcoidosis as well as HLA types linked with sarcoidosis disease course, severity, and organ involvement. For example, HLA DRB1*1501 and HLA DRB3*0101 both have been linked with increased risk for sarcoidosis in White and Black cohorts in the US.⁶ These genetic findings support the role of aberrant antigen processing and presentation in the pathophysiology of sarcoidosis.⁶

Specific and nonspecific skin manifestations of sarcoidosis demonstrate significant heterogeneity and may mimic other dermatologic diseases, earning cutaneous sarcoidosis its title as a great imitator.³ Common skin manifestations include papular sarcoidosis, characterized by multiple small macules and papules on the face or neck; plaque sarcoidosis, characterized by erythematous to violaceous plaques on the face, back, buttocks, or extremities; lupus pernio, characterized by indurated red to violaceous plaques on the nose, cheeks, or ears; and scar and tattoo-associated sarcoidosis, in which erythematous papules or nodules appear on scars or tattoos.^1,7,8

Less common manifestations include psoriasiform sarcoidosis, which is characterized by erythematous scaly plaques; hypopigmented sarcoidosis, which is identified by well-demarcated light-colored macules or papules; and Darier-Roussy sarcoidosis, which is characterized by nontender subcutaneous nodules.^1,7 Additional rare morphologies may involve ulcerative, erythrodermic, or ichthyosiform lesions.⁷

Patients also may present with nonspecific lesions such as erythema nodosum (EN), calcinosis cutis, or prurigo.¹ Of these, the most common is EN, which is seen more frequently in White patients compared with Black individuals or people of Asian descent.⁷ EN also may occur as a component of Löfgren syndrome, which is a type of acute sarcoidosis characterized by fever, bilateral hilar lymphadenopathy, arthralgias, and EN.^6,7 EN is associated with a favorable prognosis with fewer respiratory symptoms, whereas other skin lesions are associated with more extensive disease.⁷

The differential diagnosis for cutaneous sarcoidosis includes leprosy, fungal infection, cutaneous lupus, rosacea, psoriasis, and cutaneous malignancy.¹ However, because of its highly variable presentation, the diagnosis primarily is formulated according to morphology. For instance, for maculopapular lesions, the physician may additionally consider acne, lichen planus, and benign tumors, and for papulonodular lesions on scars or tattoos, the differential diagnosis also would include hypertrophic and keloid scars.¹

The diagnosis of cutaneous sarcoidosis is usually one of exclusion. Serum tests may be useful because elevated antinuclear antibody titers occur in approximately 30% of patients and serum angiotensin-converting enzyme levels are elevated in approximately 60% of patients.⁹ Diascopy also can be performed on lesions. Applying pressure to the lesion causes blanching and a characteristic yellow-brown “apple jelly” color, although this is easier to appreciate in lighter pigmented skin.⁹

Skin biopsy can aid in diagnosis, especially in discerning lesions from those of leprosy or lupus.¹ The hallmark of cutaneous sarcoidosis is the presence of noncaseating epithelioid granulomas with scant lymphocytes on histologic evaluation. Schaumann bodies or asteroid bodies may be seen.¹ When appropriate, stains for acid-fast and fungal organisms should be obtained and tissue culture performed because the histologic differential diagnosis includes multiple infections. Polarization also should be performed on specimens to assess for foreign material, but the presence of foreign material does not rule out sarcoidosis.^1,9

First-line therapy for cutaneous sarcoidosis consists of topical or intralesional corticosteroids for more limited disease and systemic corticosteroids for more extensive disease or disfiguring lesions.¹⁰ Additional nonsteroidal medications used in widespread disease include methotrexate, azathioprine, mycophenolate mofetil, hydroxychloroquine, minocycline, and thalidomide.^1,9,10 The tumor necrosis factor inhibitors adalimumab and infliximab also have been used to treat both systemic and cutaneous sarcoidosis.⁹ Given that cutaneous sarcoidosis may signify systemic disease, chest radiography, pulmonary function tests, ophthalmologic examinations, electrocardiogram, and liver function tests may be warranted to assess for multiorgan involvement.³

In this case, the lesions were biopsied to confirm a diagnosis of hypopigmented cutaneous sarcoidosis. Additional workup for involvement of other organs was negative. He was treated with clobetasol ointment to affected areas twice daily.

Tejas Joshi, BS, and Tiffaney Tran, BS, are medical students at Baylor College of Medicine; Tara L. Braun, MD, and Muneeza Muhammad, MD, are residents in the Department of Dermatology at Baylor College of Medicine; and Christopher Rizk, MD, is a dermatologist affiliated with Baylor College of Medicine in Houston, Texas.

References

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2. Sharma OP. Sarcoidosis: a historical perspective. Clin Dermatol. 2007;25(3):232-241. doi: 10.1016/j.clindermatol.2007.03.013
3. Karadag AS, Parish LC. Sarcoidosis: a great imitator. Clin Dermatol. 2019;37(3):240-254. doi: 10.1016/j.clindermatol.2019.01.005  
4. Rybicki BA, Major M, Popovich J, Maliank MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol. 1997;145(3):234-241. doi: 10.1093/oxfordjournals.aje.a009096
5. Ruocco E, Gambardella A, Langella GG, Lo Schiavo A, Ruocco V. Cutaneous sarcoidosis: an intriguing model of immune dysregulation. Int J Dermatol. 2015;54(1):1-12. doi: 10.1111/ijd.12566
6. Fingerlin TE, Hamzeh N, Maier LA. Genetics of sarcoidosis. Clin Chest Med. 2015;36(4):569-584. doi: 10.1016/j.ccm.2015.08.002
7. Heath CR, David J, Taylor SC. Sarcoidosis: are there differences in your skin of color patients? J Am Acad Dermatol. 2012;66(1):121.e1-14. doi: 10.1016/j.jaad.2010.06.068
8. Sepehri M, Carlsen KH, Serup J. Papular-nodular reactions in black tattoos as markers of sarcoidosis: study of 92 tattoo reactions from a hospital material. Dermatology. 2016;232(6):679-686. doi : 10.1159/000453315
9. Rosenbach MA, Wanat KA, Reisenauer A, White KP, Korcheva V, White CR. Non-infectious granulomas. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. Elsevier; 2018:1644-1663.
10. Wijsenbeek MS, Culver DA. Treatment of sarcoidosis. Clin Chest Med. 2015;36(4):751-767. doi: 10.1016/j.ccm.2015.08.015